Auditory evoked potentials: Synchronization and inhibition in the neonatal ventral hippocampal lesion rat model of schizophrenia
by Vohs, Jenifer Lynn, Ph.D., INDIANA UNIVERSITY, 2009, 158 pages; 3386730

Abstract:

Schizophrenia is a severe and chronic mental illness. However, its biobehavioral mechanisms are not well understood and difficult to study in humans. The use of animal models of schizophrenia and common biological measures such as auditory evoked potentials (EPs), which can be elicited in both basic and clinical studies, may play a critical role in understanding and treating this disorder. The present investigations utilized the Neonatal Ventral Hippocampal Lesion (NVHL) rat model of schizophrenia to test for EP abnormalities parallel to those observed in the disorder, including perturbed steady-state responses (ASSRs) and sensory gating. This research aimed to further validate the NVHL rat model of schizophrenia by: (1) characterizing potential auditory EP deficits (40 Hz ASSRs and sensory gating) like those observed in schizophrenia; (2) determining the ASSR frequency response characteristics of NHVL and sham rats; and (3) investigating the role of two receptor types (GABAA and NMDA) believed to be vital for ASSR generation (10 - 80 Hz) and in the pathophysiology of schizophrenia. ASSR parameters were found to be stable across time; and, while no baseline differences were detected, manipulation of the GABA A receptor by muscimol (agonist) yielded decreased ASSRs in NVHL and increased ASSRs in sham rats. Investigation of sensory gating resulted in observed abnormalities of both sensory registration and gating in NVHL rats. Finally, an optimal ASSR frequency was detected in sham rats at 50 Hz, while NVHL rats have optimal response at 20 Hz. The administration of both muscimol (GABAA agonist) and ketamine (NMDA antagonist) shifted the frequency of optimal response closer to 40 Hz. Taken together, these findings support the validity of the NVHL model of schizophrenia, indicate the importance of GABAA and NMDA receptors in ASSR generation and NVHL EP response, and set the stage for future research using these methods to further characterize schizophrenia etiology and aid in the development of novel treatment alternatives.
 
AdviserBrian F. O'Donnell
SchoolINDIANA UNIVERSITY
SourceDAI/B 70-12, p. , Jan 2010
Source TypeDissertation
SubjectsPsychobiology; Clinical psychology; Experimental psychology
Publication Number3386730
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